During acute ischemia, the effects of catecholamines can be extremely deleterious, leading to arrhythmias and extension of the zone of ischemia or infarction. Though an increase in surface beta-adrenergic receptors are felt to play a role, the mechanism is unknown. Work by the candidate over the past 14 months has shown that beta-receptors translocate during ischemia from an intracellular light vesicle fraction to the surface, where increased exposure to agonist is possible. This evidence that myocardial beta-adrenergic receptors can "move" between two subcellular compartments provides a means by which the heart may rapidly modulate its ability to respond to neuronally-released or circulating catecholamines. The principal goal is to further eludicate the mechanisms of receptor redistribution in ischemia. I will determine whether translocation of beta-receptors with ischemia is reversible with reperfusion, and then examine whether ischemia causes an externalization of alpha- or muscarinic receptors. Further experiments will explore the subcellular location and biochemical properties of the light vesicle receptors, as well as study the mechanisms that regulate, and therapeutic interventions that prevent, externalization of receptors in ischemia.